3 Treatment of Patients with CART19 CellsAutologous T cells collected by leuka- pheresis were transduced with a lentivirus encoding the anti-CD19 scFv linked to the 4-1BB (CD137) and CD3-z signaling domains.Gene-modified T cells were expanded and activated ex vivo by exposure to anti-CD3/CD28 beads.Ten patients received T-cell infusions con- taining a proportion of CART19 cells.Patients with CLL received lymphodepleting chemotherapy 4 to 7 days prior to infusion.Patients with ALL experienced chemo- refractory relapse, received 6 weeks of chemotherapy prior to infusion and did not require further lymphodepletion.CARCD28YZAP70SignalingdomainsAnti-CD19 ligand binding domainscFvaVHVLWith permission from Porter DL et al. Proc ASH 2012;Abstract 717.

11 Investigator Commentary — CAR T Cells Directed Against CD19 Induce Durable Responses and Transient CRS in Relapsed, Refractory CLL and ALLCAR-targeted therapy is designed for patients with cancer that expresses CD19. Most of the patients enrolled on this study have refractory CLL. Patients’ T cells are harvested and genetically modified with a vector that will express a receptor that targets CD19. The cells are then infused back into the patient. It’s a time-consuming and expensive procedure, but it definitely has merit. The authors have reported about 6 objective responses to date, some of which are CRs and are durable. This is a highly attractive strategy for ALL because once a patient experiences relapse we have no effective agents against this disease. I believe this strategy deserves more development in ALL. However, the challenge for this strategy in CLL is that we have some novel, easier-to-use and active agents — ibrutinib, ABT-199 — coming down the road. A few years ago this might have been the hottest strategy out there, but the field has changed so much that I’m a little skeptical that this therapy will make it to prime time in CLL.Interview with Brad S Kahl, MD, January 17, 2013